Periostin, a signal transduction intermediate in TGF-?-induced EMT in U-87MG human glioblastoma cells, and its inhibition by anthocyanidins.

ABSTRACT: Periostin is a secreted protein that is highly expressed in glioblastoma cells as compared to normal brain tissue, and is therefore considered as a potential biomarker in therapeutic modalities. Its contribution in the cancer cells invasive phenotype is, however, poorly understood. This work investigates the role of periostin in U-87 MG glioblastoma cell invasion, cell migration and in Transforming Growth Factor ? (TGF-?)-induced epithelial-mesenchymal transition (EMT). Periostin gene silencing, using small interfering RNA, decreased TGF-?-induced mesenchymal marker expression of fibronectin and vimentin, partly through reduced Smad2, Akt and Fak phosphorylation as well as U-87 MG cell invasion and migration. The effects of anthocyanidins, the most abundant diet-derived flavonoids, were examined on periostin-mediated downstream signaling pathways. Anthocyanidins were found to decrease periostin expression whether added under pre-, co- or post-treatment conditions along with TGF-?, and altered the Akt and Fak signaling pathways. These effects were similar to Galunisertib (LY2157299), a small molecule inhibitor of the TGF-? receptor I kinase. Taken together, our data demonstrate that periostin acts as a central element in TGF-?-induced EMT, which can be prevented by diet-derived anthocyanidins.

SUBMITTER: Ouanouki A 

PROVIDER: S-EPMC5955165 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature